Celastrol protects kidney against ischemia-reperfusion-induced injury in rats

Background: Ischemiaereperfusion (IR) causes various damages in renal tissues, which is exacerbated by hypoxia-induced excessive inflammation and deteriorates the prognosis of patients after kidney surgery. Celastrol is a potent inflammation inhibitor that has little toxicity. In this report, we investigated whether celastrol protects against IR-induced renal injury in rats. Materials and methods: Renal IR injury was induced by occlusion of the bilateral renal pedicles for 45 min followed by reperfusion for 6 h. Celastrol or vehicle solution was intraperitoneally injected 30 min before renal ischemia, respectively. Renal histology, function, and pro-inflammatory cytokines and mediators were assessed. The effect of celastrol on nuclear translocation of nuclear factor kappa B (NF-kappa B) was also measured. Results: Celastrol significantly suppressed elevation of the renal function markers and the lipid peroxidation level, alleviated renal tubular damage, and decreased the levels of tumor necrosis factor-alpha, interleukin-1 beta, and monocyte chemotactic protein-1 (MCP-1) messenger RNA in kidney caused by IR. Moreover, celastrol prevented IR-induced expression of pro-inflammatory mediators, which was associated with suppression of nuclear translocation of NF-kappa B subunit p65. Conclusions: Celastrol ameliorated the acute kidney injury caused by IR, which was associated with inhibiting local NF-kappa B activation and inflammation. Our findings suggest that celastrol could be useful for preventing IR-induced renal injury. (C) 2014 Elsevier Inc. All rights reserved.